Implementation and microbiological stability of dose-banded ganciclovir infusion bags prepared in series by a robotic system

Abstract

Objectives The implementation of dose-banding (DB) in centralised, pharmacy-based cytotoxic drug preparation units allows the preparation of standardised doses in series. The aim of this study was to evaluate the feasibility of DB for the prescribing of ganciclovir (GV) infusion solutions and to investigate the microbiological stability of dose-banded, automatically prepared readyto-administer GV infusion bags by media-fill simulation tests and sterility tests. Methods The frequency of prescription of GV doses was retrospectively analysed before and after implementing the DB scheme. Four dose-ranges or 'bands' and the corresponding standard doses (250, 300, 350, 400 mg) were identified. The maximum variance was set at ±10% of the individually prescribed dose. The aseptic preparation of a series of GV infusion bags was simulated with double strength tryptic soy broth as growth medium and prefilled 0.9% NaCl polyolefin infusion bags as primary packaging materials. The simulation process was performed with the APOTECAchemo robot on five consecutive days. In total, 50 infusion bags were filled, incubated and stored for 12 weeks at room temperature. The media-filled bags were visually inspected for turbidity after 2, 4, 8, 10 and 12 weeks. Following incubation, growth promotion tests were performed. During the simulation tests, airborne contamination was monitored with settle plates and microbial surface contamination with contact plates. Pooled sterility tests were performed for a series of 10 standard GV infusion bags after a 12-week storage period under refrigeration (2 °C-8 °C). results After implementation of the DB scheme, about 60% of the prescribed GV doses were prepared as standard preparations by the robotic system. The number of different GV doses was reduced by 61.8% (76 vs 29). None of the 50 media-filled bags showed turbidity after a storage period of 12 weeks, indicating the absence of microorganisms. The environmental monitoring with settle/contact plates matched the recommended limits set for cleanroom Grade A zones, except in the loading area of the robot. Media fills used for the sterility tests remained clear during the incubation period, thereby revealing sterility. Positive growth promotion tests proved the process's reliability. Conclusions A DB scheme for prescribing and preparation of standard GV infusion bags was successfully implemented. Microbiological tests of aseptic preparation of infusion bags in series by the APOTECAchemo robot revealed an adequate level of sterility and a well-controlled aseptic procedure. The sterility was maintained over extended storage periods, thereby encouraging extended beyond-use dating.

Dose banding of intravenous ganciclovir: Banding scheme proposal and audit of toxicity and efficiency

“…It also facilitates the automation of the preparation and the implementation of quality controls. 8 Moreover, the system guarantees the availability of standardized doses at any time, avoiding waiting times for nurses and patients, especially in the outpatient setting.…”

“…Preparation in small series also allows for savings in indirect costs not quantified in this study, such as time of preparation and better utilization of clean rooms, as well as the possibility of reusing bags not being administered. It also facilitates the automation of the preparation and the implementation of quality controls 8 . Moreover, the system guarantees the availability of standardized doses at any time, avoiding waiting times for nurses and patients, especially in the outpatient setting.…”

“…It must be emphasized that not all drugs are suitable for preparation through dose banding. Key determinants include extended stability of the solution to allow in advance preparation and storage and reasonable turnover of the products 3,8 . Actually, its implementation is only recommended in those mixtures with a minimum production of 250 preparations per year, 9 and when five bands can cover at least 60% of the total number of prescriptions 5…”

“…Key determinants include extended stability of the solution to allow in advance preparation and storage and reasonable turnover of the products. 3,8 Actually, its implementation is only recommended in those mixtures with a minimum production of 250 preparations per year, 9 and when five bands can cover at least 60% of the total number of prescriptions. 5 Although the dose-banding system is widely used to provide chemotherapy for oncology patients, other drugs could benefit from this strategy.…”

Viabilidade Da Administração Oral Em Pré-Formulação Composta Por Ganciclovir Com Nacl Por Tga/Dtga E DSC / Viability of Oral Administration in Pre-Formulation Composed of Ganciclovir With Nacl by Tga/Dtga and DSC

“…Sendo assim, o GCV age como inibidor competitivo e um substrato para a DNA polimerase viral (AGUILAR-GUISADO et al,2020). Este fármaco é indicado principalmente para o tratamento de infecções por CMV em pacientes imunocomprometidos e imunossuprimidos (CHUCHKOV et al, 2020;KRÄMER, FEDERICI, 2018).…”